Objective: To assess the efficacy of esketamine nasal spray plus an oral antidepressant compared with an oral antidepressant plus placebo nasal spray in delaying relapse of depressive symptoms in patients with TRD in stable remission after an induction and optimization course of esketamine nasal spray plus an oral antidepressant.
This double-blind, randomized clinical trial (A Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Adult Participants With Treatment-Resistant Depression [SUSTAIN-1]) used a randomized withdrawal design and was conducted from October 6, 2015, to February 15, 2018.
705 adults with prospectively confirmed TRD were enrolled; 455 entered the optimization phase and were treated with esketamine nasal spray (56 or 84mg) plus an oral antidepressant. After 16 weeks of esketamine treatment, 297 who achieved stable remission or stable response entered the randomized withdrawal phase.
Continued treatment with esketamine and antidepressant significantly delayed relapse compared with treatment with antidepressant and placebo (patients who achieved stable remission: HR,0.49; 95%CI,0.29-0.84;P = 0.003, number needed to treat [NNT], 6; patients who achieved stable response: HR, 0.30; 95% CI, 0.16-0.55: P ∠ 0.001, NNT, 4). According to HR estimates, treatment with esketamine and antidepressant decreased relapse risk by 51% among patients who achieved stable remission and by 70% among patients who achieved stable response compared with antidepressant and placebo.
NNT, Number Needed to Treat
Daly EJ, Trivedi MH, Janik A, et al. Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment- Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry 2019; 76 (9) : 893–903.
1- Daly EJ, Trivedi MH, Janik A, et al. Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry 2019; 76 (9) : 893–903.